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Phase 2a - Introductory Clinical Sciences > Immunology > Flashcards

Flashcards in Immunology Deck (160)
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what are some causes of secondary immunodeficiency?

nephrotic syndrome/protein-losing eteropathy - severe protein loss causing hypogammaglobulinaemia (seen in Crohn's, ulcerative colitis).
malnutrition (protein, energy) - impaired synthesis of immune system components.
immunosuppressive drugs.
some microorganisms - CMV, measles, rubella, viral hep, HIV.


what is autoimmunity?

immune response against a self-antigen.


what is autoimmune disease?

tissue damage resulting from an autoimmune response


what are the criteria to show a disease is caused by autoimmunity?

1. demonstrate immunological reactivity to a self-antigen
2. characterise/isolate the autoantigen
3. induce immunological reaction against same antigen by immunisation of experimental animals
4. show pathological changes in the organs/tissues of an actively sensitised animal


how does immunological tolerance ensure not everyone has autoimmune disease?

there will always be T cell receptors and Ig molecules produced that react to self-antigens - the T/B cells bearing these self-reactive molecules are eliminated/downregulated to make the immune system tolerant to self-antigens.
induction of specific tolerance occurs in or out of thymus (thymic tolerance/peripheral tolerance).
there must be a breakdown of tolerance for autoimmune disease to occur.


How does thymic tolerance work?

T cell development occurs in thymus - those bearing self-reactive molecules are negatively selected for. this is only partially successful.


how do regulation and suppression work in the context of peripheral tolerance?

self-reactive T cells may be actively suppressed by regulatory T cells recognising the same antigen


how does B cell tolerance (a peripheral tolerance) work?

production of self-reactive antibodies is limited by lack of T cell help for self-antigens


how might peripheral tolerance be overcome?

inappropriate access of self-antigens to APCs.
inappropriate/increased expression of co-stimulatory molecules.
alterations in way the self-molecules are presented to the immune system.


what makes peripheral tolerance more likely to be overcome, leading to autoimmune disease?

inflammation and/or tissue damage


how does "molecular mimicry" lead to a breakdown of tolerance?

structural similarity between self-proteins and microbial antigens, triggering an autoimmune response


what are some environmental triggers of autoimmunity?

UV radiation


what are the mechanisms of tissue damage in autoimmune disease?

activation of macrophages/cytotoxic T cells.
autoantibodies can also cause disease by binding to functional sites of self-antigens (e.g. hormone receptors, neurotransmitter receptors) - causing function abnormalities without damage/inflammation.


how are autoimmune diseases treated?

replacement of function of organ damaged.
suppression of autoimmune response - immunosuppression before irreversible tissue damage is vital (early detection is a challenge)


what is the complement system?

complex series of interacting plasma proteins acting as an enzymatic cascade - major effector system for antibody mediated immune reactions


what are the 3 pathways complement can be activated by?

1. classical pathway - by antibody
2. alternative pathway - by bacterial cell walls
3. lectin pathway - by mannose-binding lectin


what are the effects of complement activation?

increased vascular permeability.
chemoattraction of leukocytes.
enhanced phagocytosis.
cell lysis.


what letter is the major fragment of a complement component, and describe the functions of its active sites.

2 active sites:
triggering complex - binds to cell membranes.
other is for enzymatic cleavage of the next complement component.


how is complement activation controlled?

spontaneous decay of any exposed attachment sites. inactivation by specific inhibitors.


what is the major purpose of the complement pathway?

remove/destroy antigen - by direct lysis or by opsonisation


what are the two sequential phases of complement activation?

1. activation of C3 component
2. activation of the 'attack' or lytic pathway


what is the critical step of complement activation?

cleavage of C3 by complement-derived enzymes (C3 convertases).
C3b mediates vital activities, especially opsonisation.
C3 cleavage is achieved via 3 pathways, all generate C3 convertases but in response to different stimuli.


what activates the classical pathway of complement activation?

when binding of IgM/IgG to antigen causes conformational change in Fc of antibody, revealing C1 binding site


which types of Ig activate the classical pathway?

IgM and IgG


what occurs once C1 is activated in the classical pathway? what regulates this?

enzyme activity generated that splits C4 and C2 into a and b fragments.
regulated by C1 esterase inhibitor.


what complex is the classical pathway C3 convertase?



what is the action of C4b2b?

cleaves C3, with C3a being anaphylatoxic and chemotactic, and C3b binding to the initiating complex - C4b2b3b complex is a C5 convertase, initiating the final lytic pathway


what initiates the final lytic pathway following the classical pathway?

C4b2b3b - C5 convertase


what are the most important activators of the alternative pathway?

bacterial cell walls and endotoxin


what is responsible for innate defence against invading organisms?

the alternative pathway of the complement system